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RESEARCH ARTICLE

Optimal antiretroviral therapy for aging

Damien V. Cordery A and David A. Cooper A B
+ Author Affiliations
- Author Affiliations

A The Kirby Institute, University of New South Wales, Sydney, NSW 2010, Australia.

B Corresponding author. Email: dcooper@kirby.unsw.edu.au

Sexual Health 8(4) 534-540 https://doi.org/10.1071/SH11026
Submitted: 17 February 2011  Accepted: 31 March 2011   Published: 29 July 2011

Abstract

The introduction of highly active antiretroviral therapy (HAART) has irrevocably changed the nature of the HIV epidemic in developed countries. Although the use of HAART does not completely restore health in HIV-infected individuals, it has dramatically reduced morbidity and mortality. Increases in life expectancy resulting from effective long-term treatment mean that the proportion of older people living with HIV has increased substantially in the past 15 years. Increasing age is associated with many complications including cardiovascular disease, neurological complications, kidney and liver dysfunction, and metabolic complications such as dyslipidaemia and diabetes. HIV infection and antiretroviral drugs have also been associated with similar complications to those seen with increasing age. The increase in HIV prevalence in older age groups has not been accompanied by the development of treatment guidelines or recommendations for appropriate antiretroviral therapy or clinical management in these patients.

Additional keywords: highly active antiretroviral therapy, HIV.


References

[1]  Bhavan KP, Kampalath VN, Overton ET. The aging of the HIV epidemic. Curr HIV/AIDS Rep 2008; 5 150–8.
The aging of the HIV epidemic.CrossRef |

[2]  National Centre in HIV Epidemiology and Clinical Research (NCHECR). HIV, viral hepatitis and sexually transmissible infections in Australia, Annual Surveillance Report, 2010. Sydney: NCHECR; 2010. Available online at: http://www.nchecr.unsw.edu.au/NCHECRwebnsf/resources/SurvRep07/$file/ASR2010-rev1pdf [verified January 2011].

[3]  Centers for Disease Control (CDC). CDC HIV surveillance report, 2008. Atlanta: CDC; 2008. Available online at: http://www.cdc.gov/hiv/surveillance/resources/reports/2008report/pdf/2008SurveillanceReport.pdf [verified November 2010].

[4]  Gebo KA. HIV infection in older people. BMJ 2009; 338 b1460
HIV infection in older people.CrossRef |

[5]  Mapping HIV outcomes: geographical and clinical forecasts of numbers of people living with HIV in Australia, 2010. Sydney: NCHECR; 2010. Available online at: http://napwa.org.au/papers/2010/napwa-and-nchecr-jointly-launch-report-mapping-hiv-outcomes [verified October 2010].

[6]  Goulet JL, Fultz SL, Rimland D, Butt A, Gibert C, Rodriguez-Barradas M, et al Aging and infectious diseases: do patterns of comorbidity vary by HIV status, age, and HIV severity? Clin Infect Dis 2007; 45 1593–601.
Aging and infectious diseases: do patterns of comorbidity vary by HIV status, age, and HIV severity?CrossRef |

[7]  Carre N, Deveau C, Belanger F, Boufassa F, Persoz A, Jadand C, et al Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV-infected patients. SEROCO Study Group. AIDS 1994; 8 797–802.
Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV-infected patients. SEROCO Study Group.CrossRef |

[8]  Phillips AN, Lee CA, Elford J, Webster A, Janossy G, Timms A, et al More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts. J Acquir Immune Defic Syndr 1991; 4 970–5.

[9]  The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study group. Response to combination antiretroviral therapy: variation by age. AIDS 2008; 22 1463–73.
The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study group. Response to combination antiretroviral therapy: variation by age.CrossRef |

[10]  Silverberg MJ, Leyden W, Horberg MA, DeLorenze GN, Klein D, Quesenberry CP. Older age and the response to and tolerability of antiretroviral therapy. Arch Intern Med 2007; 167 684–91.
Older age and the response to and tolerability of antiretroviral therapy.CrossRef |

[11]  Mussini C, Manzardo C, Johnson M, Monforte A, Uberti-Foppa C, Antinori A, et al Patients presenting with AIDS in the HAART era: a collaborative cohort analysis. AIDS 2008; 22 2461–9.
Patients presenting with AIDS in the HAART era: a collaborative cohort analysis.CrossRef |

[12]  Hinkin CH, Hardy DJ, Mason KI, Castellon SA, Durvasula RS, Lam MN, et al Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse. AIDS 2004; 18 19–25.
Medication adherence in HIV-infected adults: effect of patient age, cognitive status, and substance abuse.CrossRef |

[13]  Appay V, Rowland-Jones SL. Premature ageing of the immune system: the cause of AIDS? Trends Immunol 2002; 23 580–5.
Premature ageing of the immune system: the cause of AIDS?CrossRef |

[14]  Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection. Lancet 2010; 376 49–62.
Antiretroviral therapy and management of HIV infection.CrossRef |

[15]  Cao W, Jamieson BD, Hultin LE, Hultin PM, Effros RB, Detels R. Premature aging of T cells is associated with faster HIV-1 disease progression. J Acquir Immune Defic Syndr 2009; 50 137–47.
Premature aging of T cells is associated with faster HIV-1 disease progression.CrossRef |

[16]  The Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008; 372: 293–9. 10.1016/S0140-6736(08)61113-7

[17]  Lohse N, Hansen AB, Pedersen G, Kronborg G, Gerstoft J, Sorensen HT, et al Survival of persons with and without HIV infection in Denmark, 1995–2005. Ann Intern Med 2007; 146 87–95.

[18]  Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009; 338 a3172
HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity.CrossRef |

[19]  Baker JV, Peng G, Rapkin J, Abrams DI, Silverberg MJ, MacArthur RD, et al CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS 2008; 22 841–8.
CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection.CrossRef |

[20]  Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009; 41 67–76.
Pharmacokinetics and drug metabolism in the elderly.CrossRef |

[21]  Borkan GA, Hults DE, Gerzof SG, Robbins AH, Silbert CK. Age changes in body composition revealed by computed tomography. J Gerontol 1983; 38 673–7.

[22]  Salles N. Basic mechanisms of the aging gastrointestinal tract. Dig Dis 2007; 25 112–7.
Basic mechanisms of the aging gastrointestinal tract.CrossRef |

[23]  Rhee MS, Greenblatt DJ. Pharmacologic consideration for the use of antiretroviral agents in the elderly. J Clin Pharmacol 2008; 48 1212–25.
Pharmacologic consideration for the use of antiretroviral agents in the elderly.CrossRef |

[24]  Shah SS, McGowan JP, Smith C, Blum S, Klein RS. Comorbid conditions, treatment, and health maintenance in older persons with human immunodeficiency virus infection in New York City. Clin Infect Dis 2002; 35 1238–43.
Comorbid conditions, treatment, and health maintenance in older persons with human immunodeficiency virus infection in New York City.CrossRef |

[25]  Grunfeld C. Dyslipidemia and its treatment in HIV infection. Top HIV Med 2009; 18 112–8.

[26]  Kearney F, Moore AR, Donegan CF, Lambert J. The ageing of HIV: implications for geriatric medicine. Age Ageing 2010; 39 536–41.
The ageing of HIV: implications for geriatric medicine.CrossRef |

[27]  Samaras K. Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection. J Antimicrob Chemother 2008; 61 238–45.
Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection.CrossRef |

[28]  Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353 2093–9.
Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study.CrossRef |

[29]  Hadigan C, Meigs JB, Corcoran C, Rietschel P, Piecuch S, Basgoz N, et al Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32 130–9.
Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.CrossRef |

[30]  Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20 2165–74.
Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review.CrossRef |

[31]  Gan SK, Samaras K, Thompson CH, Kraegen EW, Carr A, Cooper DA, et al Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy. Diabetes 2002; 51 3163–9.
Altered myocellular and abdominal fat partitioning predict disturbance in insulin action in HIV protease inhibitor-related lipodystrophy.CrossRef |

[32]  Noor MA, Seneviratne T, Aweeka FT, Lo JC, Schwarz JM, Mulligan K, et al Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study. AIDS 2002; 16 F1–8.
Indinavir acutely inhibits insulin-stimulated glucose disposal in humans: a randomized, placebo-controlled study.CrossRef |

[33]  Noor MA, Flint OP, Maa JF, Parker RA. Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically. AIDS 2006; 20 1813–21.
Effects of atazanavir/ritonavir and lopinavir/ritonavir on glucose uptake and insulin sensitivity: demonstrable differences in vitro and clinically.CrossRef |

[34]  Tien PC, Schneider MF, Cole SR, Levine AM, Cohen M, DeHovitz J, et al Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women’s Interagency HIV Study. AIDS 2007; 21 1739–45.
Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women’s Interagency HIV Study.CrossRef |

[35]  Bonfanti P, Giannattasio C, Ricci E, Facchetti R, Rosella E, Franzetti M, et al HIV and metabolic syndrome: a comparison with the general population. J Acquir Immune Defic Syndr 2007; 45 426–31.
HIV and metabolic syndrome: a comparison with the general population.CrossRef |

[36]  Wand H, Calmy A, Carey DL, Samaras K, Carr A, Law MG, et al Metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus after initiation of antiretroviral therapy in HIV infection. AIDS 2007; 21 2445–53.
Metabolic syndrome, cardiovascular disease and type 2 diabetes mellitus after initiation of antiretroviral therapy in HIV infection.CrossRef |

[37]  Carr A. HIV lipodystrophy: risk factors, pathogenesis, diagnosis and management. AIDS 2003; 17 S141–8.
HIV lipodystrophy: risk factors, pathogenesis, diagnosis and management.CrossRef |

[38]  Friis-Moller N, Sabin CA, Weber R, d’Arminio Monforte A, El-Sadr WM, Reiss P, et al Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003; 349 1993–2003.
Combination antiretroviral therapy and the risk of myocardial infarction.CrossRef |

[39]  Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte A, El-Sadr W, et al Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356 1723–35.
Class of antiretroviral drugs and the risk of myocardial infarction.CrossRef |

[40]  Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, et al Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008; 371 1417–26.
Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.CrossRef |

[41]  Costagliola D, Lang S, Mary-Krause M, Boccara F. Abacavir and cardiovascular risk: reviewing the evidence. Curr HIV/AIDS Rep 2010; 7 127–33.
Abacavir and cardiovascular risk: reviewing the evidence.CrossRef |

[42]  Fontas E, van Leth F, Sabin CA, Friis-Moller N, Rickenbach M, d’Arminio Monforte A, et al Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004; 189 1056–74.
Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles?CrossRef |

[43]  Aberg JA. Lipid management in patients who have HIV and are receiving HIV therapy. Endocrinol Metab Clin North Am 2009; 38 207–22.
Lipid management in patients who have HIV and are receiving HIV therapy.CrossRef |

[44]  Weber R, Sabin CA, Friis-Moller N, Reiss P, El-Sadr WM, Kirk O, et al Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med 2006; 166 1632–41.
Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.CrossRef |

[45]  van Leth F, Andrews S, Grinsztejn B, Wilkins E, Lazanas MK, Lange JM, et al The effect of baseline CD4 cell count and HIV-1 viral load on the efficacy and safety of nevirapine or efavirenz-based first-line HAART. AIDS 2005; 19 463–71.
The effect of baseline CD4 cell count and HIV-1 viral load on the efficacy and safety of nevirapine or efavirenz-based first-line HAART.CrossRef |

[46]  Chu KM, Boulle AM, Ford N, Goemaere E, Asselman V, Van Cutsem G. Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa. PLoS ONE 2010; 5 e9183
Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa.CrossRef |

[47]  Moodie EE, Pant Pai N, Klein MB. Is antiretroviral therapy causing long-term liver damage? A comparative analysis of HIV-mono-infected and HIV/hepatitis C co-infected cohorts. PLoS ONE 2009; 4 e4517
Is antiretroviral therapy causing long-term liver damage? A comparative analysis of HIV-mono-infected and HIV/hepatitis C co-infected cohorts.CrossRef |

[48]  Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE. Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease. J Am Soc Nephrol 2005; 16 2412–20.
Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease.CrossRef |

[49]  Perazella MA. Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy. Kidney Int 2010; 78 1060–3.
Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy.CrossRef |

[50]  Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis 2010; 51 496–505.
Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.CrossRef |

[51]  Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D’Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int 2010; 78 1171–7.
Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities.CrossRef |

[52]  Carr A, Miller J, Eisman JA, Cooper DA. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy. AIDS 2001; 15 703–9.
Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy.CrossRef |

[53]  Mallon PW. HIV and bone mineral density. Curr Opin Infect Dis 2010; 23 1–8.
HIV and bone mineral density.CrossRef |

[54]  Papaioannou A, Kennedy CC, Cranney A, Hawker G, Brown JP, Kaiser SM, et al Risk factors for low BMD in healthy men age 50 years or older: a systematic review. Osteoporos Int 2009; 20 507–18.
Risk factors for low BMD in healthy men age 50 years or older: a systematic review.CrossRef |

[55]  Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou A, Cheung AM, et al Risk factors for low bone mass in healthy 40–60 year old women: a systematic review of the literature. Osteoporos Int 2009; 20 1–21.
Risk factors for low bone mass in healthy 40–60 year old women: a systematic review of the literature.CrossRef |

[56]  Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Lo Y, Klein RS. Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection. AIDS 2007; 21 617–23.
Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection.CrossRef |

[57]  Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Santoro N, Schoenbaum EE. HIV infection and bone mineral density in middle-aged women. Clin Infect Dis 2006; 42 1014–20.
HIV infection and bone mineral density in middle-aged women.CrossRef |

[58]  Jones S, Restrepo D, Kasowitz A, Korenstein D, Wallenstein S, Schneider A, et al Risk factors for decreased bone density and effects of HIV on bone in the elderly. Osteoporos Int 2008; 19 913–8.
Risk factors for decreased bone density and effects of HIV on bone in the elderly.CrossRef |

[59]  Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, et al Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292 191–201.
Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.CrossRef |

[60]  Dolan SE, Kanter JR, Grinspoon S. Longitudinal analysis of bone density in human immunodeficiency virus-infected women. J Clin Endocrinol Metab 2006; 91 2938–45.
Longitudinal analysis of bone density in human immunodeficiency virus-infected women.CrossRef |

[61]  Bolland MJ, Grey AB, Gamble GD, Reid IR. Low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis. J Clin Endocrinol Metab 2007; 92 4522–8.
Low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis.CrossRef |

[62]  Grund B, Peng G, Gibert CL, Hoy JF, Isaksson RL, Shlay JC, et al Continuous antiretroviral therapy decreases bone mineral density. AIDS 2009; 23 1519–29.
Continuous antiretroviral therapy decreases bone mineral density.CrossRef |

[63]  Hansen AB, Lohse N, Gerstoft J, Kronborg G, Laursen A, Pedersen C, et al Cause-specific excess mortality in siblings of patients co-infected with HIV and hepatitis C virus. PLoS ONE 2007; 2 e738
Cause-specific excess mortality in siblings of patients co-infected with HIV and hepatitis C virus.CrossRef |

[64]  McComsey GA, Tebas P, Shane E, Yin MT, Overton ET, Huang JS, et al Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis 2010; 51 937–46.
Bone disease in HIV infection: a practical review and recommendations for HIV care providers.CrossRef |

[65]  White DA, Heaton RK, Monsch AU. Neuropsychological studies of asymptomatic human immunodeficiency virus-type-1 infected individuals. The HNRC Group. HIV Neurobehavioral Research Center. J Int Neuropsychol Soc 1995; 1 304–15.
Neuropsychological studies of asymptomatic human immunodeficiency virus-type-1 infected individuals. The HNRC Group. HIV Neurobehavioral Research Center.CrossRef |

[66]  Letendre SL, Ellis RJ, Ances BM, McCutchan JA. Neurologic complications of HIV disease and their treatment. Top HIV Med 2010; 18 45–55.

[67]  Blanch J, Martinez E, Rousaud A, Blanco JL, Garcia-Viejo MA, Peri JM, et al Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz. J Acquir Immune Defic Syndr 2001; 27 336–43.

[68]  Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, et al Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008; 65 65–70.
Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system.CrossRef |

[69]  Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, et al Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009; 23 1359–66.
Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance.CrossRef |

[70]  Winston A, Duncombe C, Li PC, Gill JM, Kerr SJ, Puls R, et al Does choice of combination antiretroviral therapy (cART) alter changes in cerebral function testing after 48 weeks in treatment-naive, HIV-1-infected individuals commencing cART? A randomized, controlled study. Clin Infect Dis 2010; 50 920–9.
Does choice of combination antiretroviral therapy (cART) alter changes in cerebral function testing after 48 weeks in treatment-naive, HIV-1-infected individuals commencing cART? A randomized, controlled study.CrossRef |



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